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PubMed2005

Structural comparisons of meptazinol with opioid analgesics.

AIM: To investigate the mechanism of action of a potent analgesic, (+/-)-meptazinol. METHODS: The structures of meptazinol enantiomers were compared with opioid pharmacophore and tramadol. RESULTS: Neither enantiomer of meptazinol fitted any patterns among the opioid pharmacophore and tramadol, although they did share some structural and pharmacological similarities. However, the structure superpositions implied that both enantiomers of meptazinol might share some similar analgesic mechanisms with typical opiate analgesics. CONCLUSION: Meptazinol should have a different mechanism of action to known analgesics, which would be helpful in further investigations of meptazinol in the search for non-addictive analgesics.

Analgesics, Opioid↗
PubMed1998

Twelve cases of analgesic headache.

Analgesic headache occurs when drugs given for the treatment of headache aggravate symptoms. The condition is well recognised in adults but has not been described before in children in whom it may be induced by mild analgesics such as paracetamol used alone. Twelve children (nine girls and three boys, aged 6 to 16.5 years) with analgesic headache (from three months to 10 years) are reported. Five children were taking paracetamol alone, six were taking paracetamol with codeine, and one child was taking ibuprofen. The abrupt withdrawal of analgesic drugs was successful in eight of the children; two had episodic migraine headaches; one had headaches but with reduced frequency; and one returned to analgesic abuse.

Acetaminophen↗
PubMed1985

Use of simple analgesics in rheumatoid arthritis.

The usefulness of anti-inflammatory drugs in rheumatoid arthritis (RA) is beyond dispute. The role of simple analgesics is less clear and has been disputed. A survey of 21 rheumatologists indicated that a majority sometimes supplemented anti-inflammatory treatment of RA with simple analgesics. A random sample of 120 RA patients treated by the same doctors revealed that 47% ranked pain relief as the most desirable objective of their treatment and 54% were taking analgesics regularly. Of those receiving analgesics as well as non-steroidal anti-inflammatory drugs 48% considered the former to be the more effective preparations. Almost half the patients on analgesics were taking drugs without the knowledge of the rheumatologists, who may have underestimated their patients' desire for pain relief.

Acetaminophen↗
PubMed2004

UK legislation on analgesic packs: before and after study of long term effect on poisonings.

OBJECTIVE: To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter. DESIGN: Before and after study. SETTING: Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002. DATA SOURCES: Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK. MAIN OUTCOME MEASURES: Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics. RESULTS: Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths. CONCLUSION: Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.

Analgesics↗
PubMed1974

Possible role of laxatives in analgesic nephropathy.

Eight out of ten of patients with analgesic nephropathy were regular and usually heavy laxative takers compared with 12 out of 200 controls from the general population and four out of 70 patients attending a renal clinic. The finding that regular laxative taking was greatly increased in patients with analgesic nephropathy suggests that this condition may often be due to the combined abuse of both laxatives and analgesics. In a series of 40 patients with rheumatoid arthritis all were found to have normal renal function and no patient took laxatives regularly. This finding would explain why analgesic nephropathy is so uncommon in patients with rheumatoid arthritis despite the fact that they are regular and heavy analgesic takers.

Adult↗
PubMed1980

Hypercholesterolaemia and hypertriglyceridaemia in patients with analgesic nephropathy.

Patients with analgesic nephropathy are reported to have a higher risk of atherosclerosis. One possible reason for this is a high incidence of hyperlipaemia in patients with analgesic nephropathy. In a retrospective study, serum cholesterol and serum triglyceride concentrations of patients with analgesic nephropathy and moderately restricted renal function were significantly higher compared to a control group with other renal diseases of similar age and degree of renal insufficiency. Hyperlipaemia in analgesic nephropathy is not explained by end-stage renal failure on one side or protein loss as in nephrotic syndrome on the other side. Some possible mechanisms for hyperlipaemia in analgesic nephropathy are discussed.

Adult↗
PubMed1989

Progression of renal failure in analgesic-associated nephropathy.

The factors that influence the progression of renal failure in analgesic-associated nephropathy (AAN) still remain to be clarified. In this study, the actual analgesic intake (N-acetyl-p-aminophenol, NAPAP, i.e. acetaminophen in urine) and progression of renal failure (1/crea method) in 127 outpatients with various renal diseases were investigated over a period of 7-150 months. AAN was diagnosed in 57 of the 127 patients (44%). The NAPAP test was positive in 21% of the 57 AAN patients and in 3% of the 70 control patients with other renal diseases (p = 0.0001). The AAN patients presented with more advanced renal insufficiency, lost more weight, and had more severe hypertension as well as a higher mortality rate than the control patients (univariate analysis). Progression of renal insufficiency, as measured by regression analysis of the reciprocal of serum creatinine versus time and expressed as clearance loss per year, was more rapid in the AAN patients who were found positive for NAPAP (6.9 +/- 5.5 ml/min/year) than in the AAN patients who were found negative (4.1 +/- 11.0 ml/min/year) or in control patients with other renal diseases (5.1 +/- 14.9 ml/min/year). Multivariate analysis showed the more rapid clearance loss to be the most discriminating factor between the AAN patients who continued analgesic abuse of phenacetin-or acetaminophen-containing drugs and AAN patients who stopped. We therefore conclude that continued analgesic abuse promotes renal insufficiency in AAN. The progression of renal failure in AAN patients who stopped abusing analgesics, however, cannot be explained within the parameters investigated, i.e. urinary tract infection, hypertension, hyperalimentation, or papillary necrosis.

Acetaminophen↗
PubMed1976

Study of a new analgesic compound in the treatment of tension headache.

The effect of a new analgesic compound (propoxyphene, acetaminophen, caffeine, hydroxyzine) was investigated in a single-blind study comparing it with plain acetaminophen administered to forty patients with tension headache. For the study, patients were assigned to one of two groups of twenty each. Starting dose for each group was one to two tablets followed by one tablet every four to six hours. The results show that 90% clinical success was obtained with the analgesic compound, while a 45% success was obtained with plain acetaminophen. This is a statistically significant difference. Side-effects observed with analgesic compound were primarily drowsiness and dizziness of mild intensity; acetaminophen caused gastro-intestinal alterations (nausea, vomiting) and dizziness of greater severity. Therapy was withdrawn in 20% of patients taking acetaminophen because of side-effects. The dosage of analgesic compound required to control each episode of tension headache was smaller than that of acetaminophen. These results can be explained by a possible potentiation of pharmacological activity of the compound's components. It can be concluded that the analgesic compound is a new and effective combination for the symptomatic treatment of tension headache.

Acetaminophen↗
PubMed1982

Analgesic drug use in an ambulatory elderly population.

Prescribed and nonprescribed analgesic use was studied in a population of 3192 elderly ambulatory subjects. Analgesic drugs were used by 44.3 percent of women and 32.6 percent of men. The most common analgesic products used were aspirin, buffered aspirin, acetaminophen, and ibuprofen. Numerous participants reported the use of multiple analgesic products. Alkaline phosphatase, lactic dehydrogenase, and blood urea nitrogen concentrations were higher in subjects reporting the use of analgesics, but total bilirubin and serum iron concentrations were lower.

Aged↗
PubMed1990

Postoperative analgesic requirements following flumazenil administration.

The effect of flumazenil (RO 15-1788) on postoperative analgesic requirements was evaluated in 30 postoperative patients. This prospective investigation was a double-blind, placebo-controlled trial in patients undergoing general anesthesia supplemented by midazolam and fentanyl or sufentanil. Patients received either flumazenil (n = 20) or placebo (n = 10) by random assignment. Analgesic requirements were measured in morphine equivalents (MEs) and were recorded for a three-hour period following the administration of flumazenil. All patients received the assigned treatment within five minutes of arrival to the postanesthesia room. Total ME requirements were 4.1 +/- 3.8 mg for the flumazenil group and 4.5 +/- 4.6 mg (p = 0.71) for the placebo group. Patient analgesic requirements were also assessed when patients were adequately alert. For the flumazenil group this time period was 6.2 +/- 12.7 minutes versus 52.9 +/- 28.4 minutes for placebo (p less than 0.01). MEs (flumazenil 4.1 +/- 3.8 mg vs. placebo 3.7 +/- 3.2 mg) were not significantly different (p = 0.57) when similar levels of consciousness were compared. The onset of pain was more rapid with flumazenil patients as evidenced by the first analgesic dose at 15.7 +/- 25.1 minutes for the flumazenil group versus 34.7 +/- 43.7 for the placebo group; however, these data were not statistically different (p = 0.144). These results suggest that flumazenil does not increase postoperative analgesic requirements during the immediate postanesthesia period; however, patients receiving flumazenil may experience an earlier onset of postoperative pain.

Adult↗
PubMed1997

Nonnarcotic analgesics: prevalence and estimated economic impact of toxicities.

OBJECTIVE: To review and compare the risks of nonnarcotic analgesic toxicities in adults and estimate the relative healthcare costs of these toxicities, since direct comparison of costs is not possible. DATA SOURCES: A MEDLINE search of the literature from 1969 to 1995 was used to identify pertinent data. Additional references were identified from articles obtained in the search. Information was obtained from prospective, retrospective, controlled, and uncontrolled studies; case reports; and review articles. DATA EXTRACTION: Estimates of annual US costs of toxicities were extrapolated and synthesized from data from diagnosis-related groups, published information about the incidence of toxicity, or local data. DATA SYNTHESIS: Chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a high incidence of acute renal toxicity and gastrointestinal toxicity. The most common problems associated with acetaminophen use are hepatoxicity after acute problems ingestion of large doses (> 10 g) or habitual use of smaller doses (< 4 g), particularly in alcoholic patients, and chronic analgesic nephropathy. Aspirin use is associated with a high incidence of gastrointestinal and acute renal toxicity in certain patient groups. Available data suggest that acetaminophen, used intermittently, remains the nonnarcotic analgesic of choice in many patient populations, including those with impaired renal function, gastrointestinal disease, and bleeding disorders. Estimated annual US costs associated with the toxicities of acetaminophen (excluding hepatotoxicity), aspirin (acute upper gastrointestinal bleeding only), and NSAIDs (excluding non-upper gastrointestinal hemorrhagic complications and hepatotoxicity) are about $51.5 million, $358.6 million, and $1.35 billion, respectively. CONCLUSIONS: Intermittent use of most nonnarcotic analgesics produces a small risk of chronic renal or hepatic toxicity. Gastrointestinal toxicity, especially upper gastrointestinal bleeding, remains a significant problem with NSAIDs and aspirin. Acetaminophen remains the nonnarcotic analgesic of choice for intermittent use by most patient groups. The toxicities associated with NSAIDs constitute about 72.6% of the total toxicities (costs $1.86 billion) caused by NSAIDs, acetaminophen, and aspirin.

Acetaminophen↗
PubMed2004

Nonprescription analgesics and their use in solid-organ transplantation: a review.

OBJECTIVE: To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. DATA SYNTHESIS: Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. CONCLUSION: A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

Analgesics↗
PubMed2001

Lack of adherence with the analgesic regimen: a significant barrier to effective cancer pain management.

PURPOSE: To evaluate oncology outpatients' level of adherence to their analgesic regimen during a 5-week period. PATIENTS AND METHODS: A random sample of 65 adult oncology outpatients with a Karnofsky performance status score of >or= 50, an average pain intensity score of >or= 2.5, and radiographic evidence of bone metastasis were recruited for this longitudinal study from seven outpatient settings. On a daily basis, patients rated their level of pain intensity and recorded pain medication intake. Adherence rates for opioid analgesics prescribed on an around-the-clock (ATC) and on an as-needed (PRN) basis were calculated on a weekly basis. RESULTS: Overall adherence rates for ATC opioid analgesics ranged from 84.5% to 90.8% and, for PRN analgesics, from 22.2% to 26.6%. No significant differences over time were found in either of these adherence rates. CONCLUSION: One factor that seems to contribute to ineffective cancer pain management is poor adherence to the analgesic regimen.

Analgesics↗
PubMed1989

[Pharmacological study of kako-bushi-matsu: analgesic action and acute toxicity].

The analgesic effect and the acute toxicity of a medical drug "kako-bushi-matsu" (S-01), which was produced through several processing of raw aconite roots, were examined in comparison with those of ibuprofen, indomethacin and aspirin. S-01 (p.o.) inhibited the acetic acid- and phenylquinone-induced writhing dose-dependently. From the ED50 values, indomethacin showed more potent inhibitory action on the phenylquinone-induced writhing than on the acetic acid-induced writhing. Ibuprofen and aspirin showed the same tendency as indomethacin. The potency of the writhing inhibition by S-01 was almost to the same degree in both writhing methods. In the tail pressure method, S-01 raised the pain threshold ratio to almost the same degree as ibuprofen did. In Randall-Selitto's method, the analgesic effect of S-01 on inflamed foot was less than that of ibuprofen. In the normal foot, S-01 raised the pain threshold ratio dose-dependently, but ibuprofen did not influence the pain threshold ratio. On adjuvant-induced arthritic pain, S-01 and ibuprofen had an analgesic action, and this action of S-01 was less than that of ibuprofen. The oral LD50 value of S-01 was more than 10,000 mg/kg in mice and rats of both sexes. The above evidence indicates that S-01 has analgesic action and suggests that the mode of the analgesic action of S-01 may differ from those of ibuprofen, indomethacin and aspirin, which inhibit prostaglandin biosynthesis.

Analgesics↗
PubMed1984

Inhibition of electrically-induced vocalization in adjuvant arthritic rats as a novel method for evaluating analgesic drugs.

A new method for the evaluation of analgesic drugs in normal rats and in rats with hyperalgesia induced by adjuvant was developed using the vocalization response as an indicator of pain due to electrical shock. It was demonstrated that at ED50 doses, nonsteroidal anti-inflammatory drugs (NSAIDs), narcotic analgesic drugs and narcotic agonist/antagonist type analgesic drugs were effective, but pure narcotic antagonist drugs. CNS-acting drugs and anti-inflammatory steroid were ineffective. Acidic NSAIDs, except aspirin, were more effective in adjuvant arthritic rats than normals but other analgesic drugs had roughly the same effect in both. It was suggested that the acidic NSAIDs specifically inhibit inflammatory pain. Moreover, the vocalization response under adjuvant treatment is useful for the quantitative measurement of analgesics.

Analgesics↗
PubMed1988

Study on the receptor subtypes mediating the analgesic action of an enkephalin analog, Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399).

The analgesic action of the enkephalin analog EK-399 (Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH) and the subtypes of the opiate receptors mediating the action were studied. The analgesic effect of subcutaneously injected EK-399 was ten times as potent as that of morphine in the rat tail flick test. EK-399 had a longer latency time and duration time than morphine. The analgesic action of EK-399 injected into the rat spinal subarachnoid space was about 800 (1800 in molar ratio) times as potent as that of morphine in the hot plate test. EK-399 had high affinities for both mu and delta opiate receptors in the rat brain receptor binding assay. The apparent pA2 values with naloxone were 7.65 for morphine and 5.98 for EK-399 in the rat tail flick test; the difference was significant. A cross tolerance between EK-399 and morphine was examined in the rat tail flick test. Although morphine tolerant rats showed no tolerance to EK-399, EK-399 tolerant rats showed a clear tolerance to morphine. These results indicate that EK-399 has a potent and long lasting analgesic effect via opiate receptors in rats. In addition to mu-receptors, delta-receptors may be involved in its analgesic mechanism.

Analgesics↗
PubMed1999

Impact of osteoarthritis and analgesic treatment on quality of life of an elderly population.

UNLABELLED: To determine the quality of life of elderly patients with osteoarthritis (OA) compared with that of their peers with no chronic illnesses and to investigate the associations between analgesic use and quality of life. SUBJECTS: Patients >65 years of age with OA taking analgesics with (n = 33) and without (n = 26) comorbidities, and control patients with no chronic illness and not taking analgesics (n = 37). METHODS: Quality of life was assessed by the SF-36 and level of pain was measured by a visual analog scale. Multiple regression analysis was used to determine the medication characteristics and additional patient factors significantly associated with SF-36 scores. RESULTS: OA patients had significantly (p < 0.05) lower scores than control patients in all quality-of-life domains. OA patient scores were lowest for the domains of role-physical, bodily pain, and physical functioning. OA patients with comorbidities also had poorer general and mental health. Pain- and analgesic-related factors were significantly (p < 0.05) associated with physical health status, reduced vitality, general health, and social functioning. A better quality of life was associated with noncompliance, fewer visits to the physician, and taking oral nonsteroidal antiinflammatory agents. Presence of adverse drug reactions and sleep disturbance did not influence SF-36 scores significantly. CONCLUSIONS: Quality of life of elderly OA patients with and without additional comorbidities was significantly poorer than that of their healthy peers, particularly in the domains associated with physical status, but also affecting vitality, social functioning, and general health. Level of pain suffered and perceived effectiveness of analgesic medication in pain control were important factors associated with quality of life.

Aged↗
PubMed2002

Crossover trial of analgesic efficacy of glucose and pacifier in very preterm neonates during subcutaneous injections.

OBJECTIVE: Very preterm newborns undergo multiple invasive procedures. Nonpharmacological interventions are valuable alternatives for pain relief during minor procedures in neonates. Oral sucrose analgesia has been widely studied in term and preterm neonates during painful procedures. The analgesic effect of oral glucose in very preterm infants has not yet been reported. The objectives of this study were to assess the analgesic effect of orally administered glucose and to determine the synergetic analgesic effect of glucose and pacifiers during subcutaneous injections in very preterm neonates using a validated behavioral acute pain rating scale. DESIGN: Two crossover trials. SETTING: One neonatal intensive care unit in a community-based general hospital. METHODS: A prospective study was conducted in 40 very preterm neonates. Each infant received 2 treatments in a crossover manner during 2 consecutive subcutaneous injections of erythropoietin. The first trial (25 infants) was intended to compare oral 30% glucose (0.3 mL) versus placebo (0.3 mL of sterile water); the second trial (15 infants) compared oral 30% glucose (0.3 mL) versus oral 30% glucose (0.3 mL) followed by sucking a pacifier. The primary outcome measure was the evaluation of pain induced by a subcutaneous injection of erythropoietin, using Douleur Aiguë Nouveau-né scale (0 no pain, 10 maximum pain). RESULTS: Twenty-four infants completed the study in the first trial and 15 in the second one. Mean (95% confidence interval [CI]) gestational age, birth weight, postnatal age, and weight at inclusion for neonates in the first and second trial were, respectively, 28.1 (95% CI: 27.3-29.0) and 29.1 (95% CI: 27.8-30.4) weeks, 1036 (95% CI: 944-1128) and 995 (95% CI: 848-1141) g, 26.4 (95% CI: 22.4-30.3) and 26 (95% CI: 22.0-29.9) days, and 1234 (95% CI: 1120-1348) and 1209 (95% CI: 1059-1359) g. In the first trial, median (interquartile) pain scores for placebo and 30% glucose, respectively, were 7 (2.5-9.75) and 4.5 (1-6). In the second trial, median (interquartile) pain scores for 30% glucose and for 30% glucose plus pacifier, respectively, were 4 (2-7) and 4 (1-6). CONCLUSIONS: A small dose of 0.3 mL of 30% oral glucose has an analgesic effect in very preterm neonates during subcutaneous injections. This effect is clinically evident because it can be detected by a behavioral pain rating scale. The synergetic analgesic effect of glucose plus sucking a pacifier is less obvious in very preterm neonates as opposed to what other studies have showed in full-term infants.

Administration, Oral↗